Inhibition of platelet arachidonic acid 12-lipoxygenase by acetylenic acid compounds.
Eighteen acetylenic fatty acids were tested as inhibitors of human platelet arachidonic acid 12-lipoxygenase. 4,7,10,13-Eicosatetraynoic (4,7,10,13-ETYA) acid emerged as the most potent compound. Additional experiments have shown that 4,7,10,13-ETYA selectively blocked the 12-lipoxygenase in washed human platelets with lesser activity against the cyclooxygenase. The ID50 value for lipoxygenase was 7.8 microM in comparison with an ID50 of 100 microM for the cyclooxygenase. The commonly used inhibitor 5,8,11,14-eicosatetraynoic acid inhibited both enzymes with equal potency. It appears that 4,7,10,13-ETYA may be a valuable lead for selective modulation of the 12-lipoxygenase pathway in platelet or other target tissues.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology / Q000031:analogs & derivatives; D000818:Animals; D001091:Arachidonate Lipoxygenases; D001792:Blood Platelets / Q000201:enzymology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D016859:Lipoxygenase Inhibitors; D008861:Microsomes / Q000201:enzymology; D012756:Sheep
D005231:Fatty Acids, Unsaturated; D016859:Lipoxygenase Inhibitors; D015117:5,8,11,14-Eicosatetraynoic Acid; C029510:4,7,10,13-eicosatetraynoic acid; D001091:Arachidonate Lipoxygenases